The advent of next-generation sequencing technologies is allowing researchers to perform studies and make discoveries which previously were not economically or technically feasible. For example, precise knowledge of the genomic sequence within neoplastic tissues can be an indicator for treatment (similar to the erbB-2 receptor gene, Her-2, for breast cancer). Although much research and development effort has gone into the core chemistries and instruments which actually produce sequence data, few new techniques have been applied to the preparation of samples for high-throughput or use in the clinic. In particular, sequencing systems that use beads as both the solid support for amplification and to help localize samples on a sequencing chip still require tedious processing by hand. As labs scale up to use the new sequencing technologies, they are very quickly realizing that the bottleneck in the operation is in the sample preparation. In this Phase II application, we propose to take the sample preparation steps far beyond the original Phase I scope of library construction. We propose to automate the entire sample preparation process, starting just after DNA fragmentation, through library construction and ending just prior to attachment to a chip. The proposed system will be compatible with a number of next generation systems which are starting to enter the market.